Orientadores: Katia Borgia Barbosa Pagnano, Afonso Celso Vigorito / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T18:14:56Z (GMT). No. of bitstreams: 1 Machado_MelissaPereira_M.pdf: 1144638 bytes, checksum: c55a80d3cce151782b16b741b0f21149 (MD5) Previous issue date: 2009 / Resumo: A leucemia mieloide crônica (LMC) e uma desordem mieloproliferativa caracterizada pela presença do cromossomo Philadelphia (Ph), resultado da fusão do gene abl e do gene bcr cujo produto e uma proteína de atividade de tirosina quinase, inibida pelo mesilato de imatinibe. O imatinibe e hoje o tratamento de primeira linha da LMC e o monitoramento molecular dos transcritos BCR-ABL e fundamental no acompanhamento dos pacientes e na detecção precoce da perda de resposta ao tratamento. O objetivo deste trabalho foi realizar a padronização do método de PCR quantitativo (RQPCR) para o monitoramento molecular dos transcritos BCR-ABL de pacientes com LMC em tratamento com imatinibe. Foram coletadas amostras de sangue periferico de pacientes com LMC para RQ-PCR ao diagnostico e a cada três meses apos o tratamento com imatinibe. Foi utilizado o método Taqman. Como gene controle foi utilizado o ABL. Foi criada uma curva standard com diluições de 108 a 103 de um plasmideo com os transcritos b3a2 e b2a2 e com ABL. As quantificações foram feitas em duplicatas, assim como a curva standard. O threshold utilizado foi de 0,05 e a eficiência foi determinada em 99%. Os resultados foram reportados como uma relação entre BCR-ABL/ABL. Para o valor de referencia basal do laboratório foram analisadas 30 amostras de pacientes ao diagnostico, e calculada a mediana, sendo esse valor 83,66%. Resposta molecular maior (RMM) foi definida como redução dos transcritos BCR-ABL em 3 log a partir do valor basal do laboratório. Os valores foram ajustados a escala internacional, usando-se um fator de conversão de 1.19. Apos a padronização do método, foram avaliados 60 pacientes com LMC, cujas amostras foram coletadas ao diagnostico e a cada 3 meses. Respostas hematológica, citogenetica maior e citogenetica completa foram obtidas em 57 (95%), 45 (75%) e 38 (63%) dos pacientes, respectivamente. Vinte e quatro de 60 pacientes atingiram a RMM (40%), numa mediana de 8,5 meses. A sobrevida global foi superior nos pacientes com RCC (100%) vs pacientes sem RCC (77%) em 48 meses. Pacientes com RCC e com RMM tiveram uma sobrevida livre de eventos superior em relação aos pacientes que não atingiram os dois tipos de reposta (100% vs 60% respectivamente) (p= 0.007). Em resumo, neste estudo demonstramos o impacto prognostico em atingir RCC e RMM e também a importância do acompanhamento molecular nos pacientes com LMC. / Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence of Philadelphia chromosome (Ph), the result of bcr and abl gene fusion, which product is a protein with kinase activity, inhibited by imatinib. Imatinib is currently the first-line treatment of CML and molecular monitoring of BCRABL transcripts is essential in monitoring of patients and for the early detection of loss of response to treatment. The aim of this study was to standardize quantitative PCR (RQ-PCR) method for molecular monitoring of BCR-ABL transcripts in patients with CML treated with imatinib. Peripheral blood samples from chronic phase patients were collected for RQ-PCR at diagnosis and every three months after treatment with imatinib. Taqman method was used for RQ-PCR. A standard curve with dilutions of 108 to 103 of a plasmid with the b3a2 and b2a2 transcripts and ABL gene, used as the control gene, was constructed. The runs were made in duplicates. The threshold used was 0.05 and the efficiency was determined as 99%. The results were reported as a BCR-ABL/ABL ratio (%). For the reference value of the baseline of the laboratory 30 samples from patients at diagnosis were quantified and the median value calculated was 83.66%. Major molecular response (MMR) was considered a three log reduction from the baseline value. MMR values were adjusted to international scale, using a conversion factor of 1.19. After standardization, BCR-ABL levels of 60 CML patients in chronic phase treated with imatinib were measured at diagnosis and then every three months. Hematological, major cytogenetic and complete cytogenetic responses were achieved in 57 (95%), 45 (75%) and 38 (63%) patients, respectively. Twenty-four out of 60 patients achieved a MMR (40%), in a median time of 8.5 months. Overall survival was superior for patients with CCR (100%) versus patients with no CCR (77%) (p= 0.01) in 48 months. Patients with CCR and with MMR had a superior event free-survival (EFS) in comparison with patients with CCR and no MMR (p= 0.007). In conclusion, we could demonstrate the prognostic impact of achieving CCR and a major molecular response and also the importance of molecular monitoring in the follow-up of CML patients. / Mestrado / Ciencias Medicas / Mestre em Clinica Medica

Chez les oiseaux, les espèces aux aptitudes cognitives avancées, et celles faisant face aux coûts et aux bénéfices de la vie en groupe, sont particulièrement intéressantes pour étudier l'émergence de formes complexes de socialité. Dans ma thèse, j'ai étudié les mécanismes comportementaux sous-jacents à la diversité et la dynamique des relations sociales dans un groupe de corbeaux freux captifs, une espèce de corvidé monogame et coloniale. J'ai montré que les freux peuvent former des relations en dehors du contexte reproducteur et changer de partenaire au cours de leur vie. De plus, j'ai montré : une certaine résilience de la structure sociale face aux variations temporelles des relations, de la composition du groupe et du sex-ratio; et l’absence d’effets stabilisateurs des relations de dominance sur la structure. Mon travail démontre que la structure sociale chez le corbeau freux est plus qu’un simple agrégat de paires, et forme la base d’une organisation sociale aux multiples niveaux. / Numerous avian species are good candidates to study the emergence of complex forms of sociality, in particular the species showing advanced cognitive skills, and the one living in groups all year long, coping with the costs and benefits of group living. In my thesis, I investigated the proximate mechanisms underlying the diversity and dynamic of social relationships in captive adult rooks, a colonial and monogamous corvid species. I found that rooks have the ability to form non-reproductive social bonds and several pair bonds throughout their life. In addition, I found: that the group social structure was flexible enough to allow temporal variations of relationships, group composition and sex-ratio; and that dominance relationships do not have any long lasting effects on the stabilisation of the structure. Overall, my work demonstrates that rooks social structure extends far beyond a simple aggregation of reproductive pairs, and may be acknowledged as a multi-level social organisation.

La gestion de ressources distribuées à l'échelle planétaire dans plusieurs organisations virtuelles implique de nombreux défis. Dans cette thèse, nous proposons un modèle pour la gestion dynamique de services dans un environnement de grille pair-à-pair à large échelle.Ce modèle, nommé P2P4GS, présente l'originalité de ne pas lier l'infrastructure pair-à-pair à la plate-forme d'exécution de services.De plus, il est générique, c'est-à-dire applicable sur toute architecture pair-à-pair. Pour garantir cette propriété, vu que les systèmes distribués à large échelle ont tendance à évoluer en termes de ressources, d'entités et d'utilisateurs, nous avons proposé de structurer le système de grille pair-à-pair en communautés virtuelles (clusters).L'approche de structuration est complètement distribuée et se base uniquement sur le voisinage des noeuds pour l'élection des responsables de clusters appelés PSI (Proxy Système d'Information). D'autre part, afin de bien orchestrer les communications au sein des différentes communautés virtuelles et aussi permettre une recherche efficace et exhaustive de service, lors de la phase de structuration, un arbre couvrant constitué uniquement des PSI est maintenu. Les requêtes de recherche vont ainsi être acheminées le long de cet arbre.Outre la découverte de services, nous avons proposé des mécanismes de déploiement, de publication et d'invocation de services. Enfin, nous avons implémenté et analysé les performances de P2P4GS. Afin d'illustrer sa généricité, nous l'avons implémenté sur Gia, Pastry et Kademlia des protocoles pair-à-pair opérant de manières totalement différentes.Les tests de performances ont montré que le P2P4GS fournit une bonne résistance aux pannes et garantit un passage à l'échelle en termes de dimensionnement du réseau et également de coût de communications. / Resource management management worldwide distributed in several virtual organizations is a key issue.In this thesis, we propose a model for dynamic services management in large-scale peer-to-peer Grid environments.This model named P2P4GS, presents originality not to link peer-to-peer infrastructure to the execution services platform.In addition, the middleware is generic i.e. it able to be applied on any peer-to-peer architecture.Meanwhile, the increasing size of resources and users in large-scale distributed systems has lead to a scalability problem.To ensure scalability, we propose to organize the peer-to-peer Grid nodes in virtual communities so called clusters.The structuring approach is completely distributed, and only requires local knowledge about nodes neighborhood for election of cluster managers called ISP (Information System Proxy).On the other hand, in order orchestrate communications in the various virtual communities and also enable an efficient service discovery,during structuring process, a spanning tree only constituted of ISP is maintained. Therefore, search queries will be routed along the spanning tree.Besides the service discovery, we proposed service deployment, publication and invocation mechanisms.Finally, we implemented and analyzed the performance of P2P4GS.To illustrate that P2P4GS is generic, we implemented protocols that operating in fully different way. These protocols are Gia, Pastry and Kademlia.Performance tests show that, on the one hand, our approach provides good fault tolerance and ensures the scalability in terms of the clusters distribution and communication cost.

La recherche et l'indexation de données en fonction d'une date ou d'une zone géographique permettent le partage et la découverte d'informations géolocalisées telles que l'on en trouve sur les réseaux sociaux comme Facebook, Flickr, ou Twitter. Cette réseau social connue sous le nom de Location Based Social Network (LBSN) s'applique à des millions d'utilisateurs qui partagent et envoient des requêtes ciblant des zones spatio-temporelles, permettant d'accéder à des données géolocalisées générées dans une zone géographique et dans un intervalle de temps donné. Un des principaux défis pour de telles applications est de fournir une architecture capable de traiter la multitude d'insertions et de requêtes spatio-temporelles générées par une grande quantité d'utilisateurs. A ces fins, les Tables de Hachage Distribué (DHT) et le paradigme Pair-à-Pair (P2P) sont autant de primitives qui forment la base pour les applications de grande envergure. Cependant, les DHTs sont mal adaptées aux requêtes ciblant des intervalles donnés; en effet, l'utilisation de fonctions de hachage sacrifie la localité des données au profit d'un meilleur équilibrage de la charge. Plusieurs solutions ajoutent le support de requêtes ciblant des ensembles aux DHTs. En revanche ces solutions ont tendance à générer un nombre de messages et une latence élevée pour des requêtes qui ciblent des intervalles. Cette thèse propose deux solutions à large échelle pour l'indexation des données géolocalisées. / Indexing and retrieving data by location and time allows people to share and explore massive geotagged datasets observed on social networks such as Facebook, Flickr, and Twitter. This scenario known as a Location Based Social Network (LBSN) is composed of millions of users, sharing and performing location-temporal range queries in order to retrieve geotagged data generated inside a given geographic area and time interval. A key challenge is to provide a scalable architecture that allow to perform insertions and location-temporal range queries from a high number of users. In order to achieve this, Distributed Hash Tables (DHTs) and the Peer-to-Peer (P2P) computing paradigms provide a powerful building block for implementing large scale applications. However, DHTs are ill-suited for supporting range queries because the use of hash functions destroy data locality for the sake of load balance. Existing solutions that use a DHT as a building block allow to perform range queries. Nonetheless, they do not target location-temporal range queries and they exhibit poor performance in terms of query response time and message traffic. This thesis proposes two scalable solutions for indexing and retrieving geotagged data based on location and time.

The thesis presents a method of the delimiter based syntax analysis. There is introduced a definition, an algoritm of the computation and analysis of the delimiters in the thesis. Farther the thesis presents an algorithm creating a distributed parser based on the input grammar with the analysed delimiter symbols. Then there is introduced an implementation of the distributed parser created by the introduced method.

The antiferromagnetic semiconductor MnTe has recently attracted significant interest as a potential high-performance thermoelectric material. Its promising thermoelectric properties are due in large part to short-range magnetic correlations in the paramagnetic state, which enhance the thermopower through the paramagnon drag effect. Using magnetic pair distribution function (mPDF) analysis of neutron total scattering data, we present a detailed, real-space picture of the short-range magnetic correlation in MnTe, offering a deeper view into the paramagnon drag effect and the nature of the correlated paramagnetic state. We confirm the presence of nanometer-scale antiferromagnetic correlations far into the paramagnetic state, show the evolution of the local magnetic order parameter across the N\'eel temperature T_N=307 K, and discover a spatially anisotropic magnetic correlation length. By combing our mPDF analysis with traditional atomic PDF analysis, we also gain detailed knowledge of the magnetostructural response in MnTe. We observed a spontaneous volume contraction of nearly 1\%, the largest spontaneous magnetovolume effect reported so far for any antiferromagnetic system. The lattice strain scales linearly with the local magnetic order parameter, in contrast to the quadratic scaling observed for the conventional magnetostriction properties of this technologically relevant material. Using neutron and X-ray PDF analysis, we also investigated the local distortion on MnTe and Mn-based systems, MnS and MnO as a function of temperature. Such local distortion on MnTe increases with the rise in temperature and becomes more pronounced at 500 K.

Distributed methods of working with software development grow larger each and every day. One of these methods is distributed pair programming. The problem is that because of the large amount of different tools there is to choose from when working remotely, it may be difficult for developers to know what they should pick, in order for their work to be as effective and enjoyable as possible, when working with distributed pair programming. This thesis investigates how different tools and practices used when working with distributed pair programming has been experienced previously by people working or studying in areas related to software development. Further the goal is to also provide recommendations about what tools and practices should be used for future work with distributed pair programming. From the results of this thesis the following recommendations could be made. Discord is recommended for communication if the use of face cam is not very important, and Zoom is recommended if it is. These tools are also recommended for screen sharing. For code sharing Git should be used, and it is also strongly recommended that the developers get comfortable with using Git as early as possible. For a shared text editor Visual studio live share or Teletype for Atom is recommended, however one should not put to much work into making the shared text editor function, since this does not necessarily have a large positive impact on the development. / Användning av distribuerade metoder under mjukvaruutveckling ökar för var dag. En av dessa metoder är distribuerad parprogrammering. Problemet är att på grund av den stora mängd olika verktyg som finns att välja bland när man arbetar på distans, så kan det vara svårt för utvecklare att veta vilka verktyg de bör välja, för att deras arbete ska vara så effektivt och en så bra upplevelse som möjligt, när de arbetar med distribuerad parprogrammering. Denna uppsats undersöker hur olika verktyg och metoder som används vid arbete med distribuerad parprogrammering upplevs av utvecklare som arbetar med eller studerar inom ett fält relaterat till mjukvaruutveckling. Målet är att ge rekommendationer om vilka verktyg och metoder som bör användas i framtiden när man arbetar med distribuerad parprogrammering. Från resultatet i denna uppsats kunde följande rekommendationer göras. Discord rekommenderas för kommunikation ifall utvecklarna inte känner starkt behov av att kunna se varann, och Zoom rekommenderas ifall utvecklarna känner att dem har ett stort behov av detta. Dessa verktyg rekommenderas även för skärmdelning. För koddelning så rekommenderas Git, och det rekommenderas även starkt att utvecklarna lär sig detta så tidigt som möjligt. För en delad textredigerare så rekommenderas Visual studio live share eller Teletype för Atom, men utvecklarna bör inte lägga för mycket tid på att försöka få detta att fungera, då detta inte nödvändigtvis har en stor positiv inverkan på arbetet.

This thesis expands our understanding of the role of several different mating behaviours in the process of forming and maintaining human mating pair-bonds. Chapter 2 investigated within-sex mating strategies and found that their distribution reflects the presence of two phenotypes, one favouring the pursuit of short-term mating and one the establishment of mating pair-bonds, each driven by prenatal testosterone exposure. Chapter 3 investigated the possible functional role of kissing in mating relationships, and found that it was utilised divergently by individuals pursuing different mating strategies, with those interested in short-term mating utilising it to assess the suitability of potential mates at initial relationship stages, and those interested in long-term mating using it to mediate pair-bond attachments. Chapter 4 examined female attitudes towards kissing across the menstrual cycle and found that attitudes varied with cycle phase, mediated by fluctuations in the hormone progesterone. This chapter also investigated the effects of kissing-related information on mate assessment and found that such information influenced mate desirability, even in the presence of typically dominant visual cues. Lastly, Chapter 5 investigated the cognitive effects of established pair-bonds, finding that individuals ‘in love’ with a mating partner show improved empathising abilities, particularly males when it comes to assessing negative emotional states in others. Using an evolutionary framework, each chapter of this thesis contributes novel insights to our understanding of these diverse behaviours. These results suggest that that future research must take into account within-sex phenotypic differences in order to truly understand human mating strategy decisions, and that different mating strategy phenotypes might adaptively utilise the same courtship behaviours in divergent ways. Furthermore, these results also suggest that pair-bonding in humans may be a relatively recent phenomenon, and that the formation of such pair-bonds can have adaptive cognitive effects for males within such bonded relationships.

In this project we investigate the feasibility of detecting the signatures of Pop III stars in metal poor second generation stars and in gas clouds at high redshifts. First, the nucleosynthetic yields of Pair Instability Supernova and how they are manifested in gas clouds are presented. Next, some basic quantities of radio astronomy are explained and the requirements of SKA are shown. Then, the minimum detectable hydrogen column density of SKA for gas clouds at high redhsift is calculated and after that the basic principles of spectroscopy and the requirements of the HiReS instrument of E-ELT are demonstrated. Finally, suggestions about where the observations with HiReS should focus are made.

This thesis examines interactional dimensions of the 2008 U.S. presidential debates based on the conversation analytic concepts of sequence organization and turn management. Drawing on the video recordings of the three 2008 presidential debates, I investigate features of turn design and interactional strategies that candidates employ during the debates and compare stylistic differences between John McCain and Barack Obama. I first examine how candidates design their first-turn responses to the moderator’s question in terms of placement of two different actions, answer and attack. Secondly, I focus on design of the second-turn responses and examine how candidates show responsiveness to both the moderator’s question and the opponent’s prior turn by incorporating multiple actions (e.g., attack, defense, and answer) in their second turns. I also examine direct exchanges between McCain and Obama, particularly concerning their strategic use of the record and their interactional practices in claiming turns and managing overlapping talk in confrontation sequences. My analysis shows that some stylistic differences exist between McCain’s and Obama’s turns. I provide detailed description of how Obama makes a systematic transition from answer to attack in his first-turn responses, which is distinguished from McCain’s first turns in which attacks are inserted in his answer as relevant topics are brought up. My analysis of the second-turn responses shows that McCain frequently produces an attack at turn beginning or responds to an attack with a reciprocal attack before producing a defense, while Obama tends to produce a defense first and then move to an attack. Lastly, I discuss how both Obama and McCain manage their turns and use turn-taking techniques to avoid direct references to their own record and shift the focus of the talk to the opponent’s stance on a related issue. / text